- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02760121
AZ, MZ, and the Pulmonary System Response to Hypoxia
October 18, 2016 updated by: University of British Columbia
The Effect of Carbonic Anhydrase Inhibitors on the Pulmonary System Response to Hypoxia
The purpose of this proposal is to compare the physiological effects of acetazolamide (AZ) and methazolamide (MZ) on the control of breathing and hypoxic pulmonary vasoconstriction.
The first objective is to assess the effects of AZ and MZ on the control of breathing in normoxia and hypoxia.
To achieve this the ventilatory interaction between oxygen and carbon dioxide will be measured and effects compared between placebo, AZ, and MZ conditions.
In addition, the isocapnic and poikilocapnic hypoxic ventilatory response and hypercapnic ventilatory response will be measured with each drug.
The second objective is to assess the effects of AZ and MZ on the control of the pulmonary vasculature during hypoxia.
Pulmonary pressure and cardiac output will be measured during 60 minutes of poikilocapnic hypoxia.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
14
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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British Columbia
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Kelowna, British Columbia, Canada, V1V 1V7
- University of British Columbia
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 38 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Male
Description
Inclusion Criteria:
- 18-40 years of age
- regularly physically active
- male
Exclusion Criteria:
- ex-smokers
- pulmonary function <80% of predicted
- contraindications to carbonic anhydrase inhibitors (eg. severe or absolute glaucoma, adrenocortical insufficiency, hepatic insufficiency, renal insufficiency, sulfa allergy or an electrolyte imbalance such as hyperchloremic acidosis)
- Obese (BMI>30Kg/m2)
- diuretic medication use
- blood thinner use
- anti-platelet drug use.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Acetazolamide
Participants will be dosed 250mg Acetazolamide (p.o.) three times per day for two days prior to and a single dose on the day of study.
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Experimental: Methazolamide
Participants will be dosed 100mg Methazolamide (p.o.) twice daily separated by a placebo for two days prior to and a single dose on the day of study.
The placebo dose is provided to match the dosing schedule between conditions.
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Placebo Comparator: Placebo
Participants will take (p.o.) placebo pills three times per day for two days prior to and a single dose on the day of study.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in ventilation
Time Frame: Baseline and 60 minutes of poikilocapnic hypoxia
|
To quantify the isocapnic hypoxic ventilatory response, the hypercapnic ventilatory response, and the hypercapnic hypoxic ventilatory response, ventilation will be measured throughout controlled changes in end-tidal gas levels.
Each protocol will consist of 90s steps in end-tidal oxygen partial pressure from baseline through 65, 57, and 47 mmHg.
For hypercapnic hypoxia, the end-tidal partial pressure for carbon dioxide will be increased from baseline to +6 mmHg for 7 minutes before reducing the end-tidal partial pressure of oxygen as above.
The poikilocapnic hypoxic ventilatory response will be determined by measuring the change in ventilation from baseline throughout 60 minutes of poikilocapnic hypoxia (fraction of inspired oxygen = 0.12)
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Baseline and 60 minutes of poikilocapnic hypoxia
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Change in pulmonary artery pressure
Time Frame: Baseline and 60 minutes of poikilocapnic hypoxia
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Pulmonary artery systolic pressure (PASP) will be derived using the modified Bernoulli equation and the regurgitant velocity across the tricuspid valve.
Estimates of right atrial pressure will be evaluated based upon the collapsibility index of the inferior vena cave during a sniff test.
The pulmonary artery pressure response will be measured during 60 minutes of exposure to poikilocapnic hypoxia (fraction of inspired oxygen = 0.12)
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Baseline and 60 minutes of poikilocapnic hypoxia
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in cerebral blood velocity
Time Frame: Baseline and 60 minutes
|
To quantify the isocapnic hypoxic cerebral blood velocity response, the hypercapnic cerebral blood velocity response, and the hypercapnic hypoxic cerebral blood velocity response, cerebral blood velocity in the middle and posterior cerebral arteries will be measured throughout controlled changes in end-tidal gas levels.
Each protocol will consist of 90s steps in end-tidal oxygen partial pressure from baseline through 65, 57, and 47 mmHg.
For hypercapnic hypoxia, the end-tidal carbon dioxide partial pressure will be increased from baseline to +6 mmHg for 7 minutes before reducing the end-tidal oxygen partial pressure as above.
The poikilocapnic hypoxic ventilatory response will be determined by measuring the change in ventilation from baseline throughout 60 minutes of poikilocapnic hypoxia (fraction of inspired oxygen = 0.12)
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Baseline and 60 minutes
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
change in arterial oxygen partial pressure
Time Frame: Baseline and 60 minutes
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Baseline and 60 minutes
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Change in arterial carbon dioxide partial pressure
Time Frame: Baseline and 60 minutes
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Baseline and 60 minutes
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Change in arterial pH
Time Frame: Baseline and 60 minutes
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Baseline and 60 minutes
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Change in heart rate
Time Frame: Baseline and 60 minutes
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Baseline and 60 minutes
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change in blood pressure
Time Frame: Baseline and 60 minutes
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Baseline and 60 minutes
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change in end-tidal oxygen and carbon dioxide partial pressure
Time Frame: Baseline and 60 minutes
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Baseline and 60 minutes
|
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Change in arterial oxygen saturation
Time Frame: Baseline and 60 minutes
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Baseline and 60 minutes
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Change in cardiac output
Time Frame: Baseline and 60 minutes of poikilocapnic hypoxia
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Cardiac output will be determined using the aortic time integral velocity and the diameter of the aortic valve annulus.
Data will be collected at baseline and throughout exposure to poikilocapnic hypoxia (fraction of inspired oxygen = 0.12)
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Baseline and 60 minutes of poikilocapnic hypoxia
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Change in pulmonary venous blood velocity
Time Frame: Baseline and 60 minutes of poikilocapnic hypoxia
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Doppler ultrasound will be used to measure the velocity of blood draining from the pulmonary vein at baseline and throughout exposure to poikilocapnic hypoxia (fraction of inspired oxygen = 0.12)
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Baseline and 60 minutes of poikilocapnic hypoxia
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Hemoglobin
Time Frame: Baseline
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Baseline
|
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albumin
Time Frame: Baseline
|
Baseline
|
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iron
Time Frame: Baseline
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Baseline
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
May 1, 2016
Primary Completion (Actual)
August 1, 2016
Study Completion (Actual)
August 1, 2016
Study Registration Dates
First Submitted
April 20, 2016
First Submitted That Met QC Criteria
May 2, 2016
First Posted (Estimate)
May 3, 2016
Study Record Updates
Last Update Posted (Estimate)
October 19, 2016
Last Update Submitted That Met QC Criteria
October 18, 2016
Last Verified
October 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Respiratory Tract Diseases
- Respiration Disorders
- Lung Diseases
- Signs and Symptoms, Respiratory
- Hypertension
- Altitude Sickness
- Hypertension, Pulmonary
- Hypoxia
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Carbonic Anhydrase Inhibitors
- Natriuretic Agents
- Diuretics
- Anticonvulsants
- Acetazolamide
- Methazolamide
Other Study ID Numbers
- H16-00028
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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